Correspondence: Ms L. Mårtensson, Department of Health Sciences, University of Skövde, Sweden, Box 408, SE-541 28 Skövde, Sweden.
Objective To investigate whether, during injections of sterile water, there is any difference in perceived pain between intracutaneous and subcutaneous injections.
Design Blind controlled trial with cross-over design.
Setting Göteborg and Skövde, Sweden.
Participants One hundred healthy female volunteers.
Methods The women were randomised into two groups and subjected to two trials, within one week of each other. During the first trial one group (n= 50) received the intracutaneous injection first, followed by the subcutaneous injection. The second group (n= 50) was given the subcutaneous injection first, followed by intracutaneous injection. In both groups all the injections were given in reverse order during the second trial.
Main outcome measures Experienced pain during the administration of sterile water injections, measured by visual analogue scale.
Results The analysis showed intracutaneous injections to be significantly more painful than subcutaneous injections, even after adjusting for injection day and for left/right site of injection (mean 60.8 vs 41.3, P < 0.001).
Conclusions The findings suggest that the less painful subcutaneous injection technique should be used.
Many women suffer from severe lower back pain during the first stage of labour, which is presumed to be referred pain from the cervix and corpus uteri1. It has been reported that approximately 30% of all women in labour suffer continuous lower back pain, the effect of which is tiring and exhausting. Continuous pain is more difficult to cope with as the parturient lacks the normal painless intervals necessary for resting between the contractions2. There are numerous ways to treat labour pain with pharmacological as well as nonpharmacological methods. Some pharmacological methods, for example narcotics and entonox, provide general analgesia. Drowsiness, nausea, vomiting and a perceived loss of control3 are among the negative side effects. Narcotics are also known to provide a limited level of pain relief and their effect is mainly due to sedation4. Furthermore, they may cause neonatal respiratory depression5,6. Various blockades (i.e. epidural and saddle (pudendal) block7) are alternative pain relief methods. Epidural analgesia is the most potent of all pain relief methods for labour pain, but negative side effects such as an increased risk for immobility, prolonged labour and instrumental deliveries have been demonstrated5,8.
Due to the risk of losing control or to potentially negative neonatal effects, many women do not want to use pharmacological pain relief methods even when they are offered. Furthermore, besides epidural analgesia, none of the methods mentioned here have proved efficient for lower back pain. For this type of pain, cutaneous injections of sterile water have shown to provide good analgesia.
In previous studies cutaneous injections of sterile water have been shown to relieve pain following whiplash injuries9,10 and chronic myofascial pain11. Pain from visceral organs projected to a skin area, such as pain from ureter stones12 or labour pain13–15, has also been treated effectively by sterile water injections. The sterile injection method is very simple to use, for instance for women in labour, who frequently suffer from back pain1. It has been used in the Scandinavian countries, as well as elsewhere15–17. It was introduced in Sweden in 1986 and has rapidly been implemented in all maternity wards in the country18. However, a drawback of the method is the transient intense pain experienced for approximately 20–30 s at the time of injection. The water is salt-free and probably induces an osmotic gradient in the skin19, as well as a distension of the superficial cell layers. Various modifications of the technique have recently been tried in order to reduce pain during administration, which can be especially intolerable for patients with musculosceletal pain syndromes who often receive a large number of injections at each treatment11. A modification, using the subcutaneous instead of the intracutaneous technique, has also been tried for parturition pain with preserved analgesic effect20. However, during that particular trial we were not able to confirm that the subcutaneous injection technique was less painful than the intracutaneous technique. We have conducted a clinical trial with female healthy volunteers so as to not confound the injection pain with the labour pain. The aim of the present study was to investigate if, during injections of sterile water, there is any difference in perceived pain between intracutaneous and subcutaneous injections.
The study included 100 apparently healthy female volunteers who took part in a blind, controlled trial with cross-over design. The cross-over design was chosen as comparisons ‘within-subject’ instead of ‘between-subjects’ are preferable when pain assessments are the case. Pain is experienced highly individually and comparisons within subjects give more information about the actual effect of the treatment21. In order to detect a difference of 10 mm on a usual analogue pain scale with a power of 85 percent, at a 5 percent significance level, the sample size would have to be 90 subjects. Our sample of 100 subjects is thus justified.
The inclusion criteria were: age from 18 to 45, non-pregnant and no other pain experienced during the trial. Subjects were recruited among obstetricians, midwives, nurse assistants and nurse students at the Departments of Obstetrics and Gynaecology at Mölndal Hospital and KSS Hospital in Skövde, and at the department of health sciences at the University of Skövde. We chose only women of childbearing age since labour pain relief is our main area of interest. They were all given both verbal and written information about the trial. The study was approved by the Research Ethics Committee of the Medical Faculty at the University of Göteborg.
The women were randomised by computer into two groups and subjected to two trials within one week of each other. A sealed envelope was opened by one of the two midwives who performed the trial, just before the administration of the injections. The result of the randomisation was known only to that midwife.
One group (n= 50) received the intracutaneous injection first and the subcutaneous injection about 10 minutes later during the first trial. The injections were given in reverse order on the second trial within one week. The second group (n= 50) was given the subcutaneous injection first and the intracutaneous injection about 10 minutes later during the first trial and the injections were given in reverse order on the second trial. None of the women were aware of which injection type they were given. In all cases, a 1 mL plastic syringe (Codan Medical, Denmark) with a thin needle (diameter 0.4 mm, length 19 mm) (Becton Dickinson, Ireland) was used. The amount of sterile water given was 0.1 mL in the intracutaneous injections and 0.5 mL in the subcutaneous injections. All injections were given by two midwives with extensive experience of both intracutaneous and subcutaneous injection techniques.
The subject was given one injection over the left side of the sacrum, and after 1.5 minutes she ranked her pain on a ungraded horizontal 100 mm visual analogue scale. The scale ranged from ‘no pain’ to ‘worst conceivable pain’. The procedure was repeated after about 10 minutes on the right side over the sacrum. Means of the two rankings of the pain during the intracutaneous and subcutaneous injections, respectively, were calculated for each subject and for day of trial. A general linear model for repeated measures was applied. Tests of statistical significance were performed against the null hypothesis that there was no difference in perceived pain between intracutaneous and subcutaneous injections. The SPSS (Statistical Package for the Social Sciences) was used for the statistical analyses.
Among the 100 women, 12 ranked the pain from the subcutaneous injection to be most painful, four did not experience any difference between the two techniques and 84 found intracutaneous to be most painful. The distribution of differences in pain rankings is shown in Fig. 1. According to a general linear model for repeated measures, the women experienced the first day's injections as more painful than the second day's injections (mean 53.7 vs 48.5, P < 0.001). Furthermore, the analysis showed intracutaneous injections to be significantly more painful than subcutaneous injections, even after adjusting for injection day and for left/right site of injection (mean 60.8 vs 41.3, P < 0.001).
When studying pain relief methods, it is relevant to question how much less painful the experience becomes after the treatment in question. As experience of pain is individual and subjective, it is difficult and even questionable whether comparisons between different subjects are meaningful. This was the reason for choosing the cross-over design with ‘within-subject’ comparisons. The visual analogue scale system is not created to quantify exactly the pain experienced and it is therefore not meaningful to calibrate the scale. In this particular case, the women perceived one of two different injection techniques to be less painful than the other. Since the methods are comparable in terms of cost, time and access, there is reason to prefer the less painful technique even though there is no exact quantification of the decrease in perceived pain.
The present study indicates that subcutaneous injections of sterile water are less painful than intracutaneous injections. The potential confounding effect of the first injection being more painful than the second, due to the subject's expectations of the injections to be painful, was controlled for by randomising the two injection techniques to the first and second trials, respectively. At the second trial, the subjects were better prepared for the induction of pain and might have coped with more ease.
Earlier scientific results show that besides intracutaneous injections, subcutaneous injections of sterile water are effective as well in treating pain following whiplash injuries9,10 and lower-back pain during labour20. Musculosceletal pain is often associated with tender and trigger points, which are often used as injection sites. As many injections are required, often > 30, some patients cannot tolerate the injection pain. For that reason Byrn et al.9,10 changed from using intracutaneous to subcutaneous technique. However, this change was based on clinical experience, not on controlled studies. Treating acute pain such as labour pain with only a few injections is most often acceptable for the woman14. Some women though experience the pain from intracutaneous injections as so hard to cope with that they, in spite of good pain relief for the labour pain, do not want to repeat the treatment17,18.
The analgesic mechanism of action is unclear but the ‘gate control’ theory22 may provide explanations. Somatic afferent stimulation by low frequency transcutaneous electrical nerve stimulation and acupuncture has been shown to activate ergoreceptors in a similar manner as muscular contractions during physical activity23. Increased pain threshold as well as increased serum concentrations of beta-endorphin and beta-lipoprotein have been shown both during somatic afferent stimulation24 and forceful muscle exercise23. This stimulation is mostly described as relaxing, pleasant and not painful at all. However, transcutaneous electrical nerve stimulation has been shown not to be effective in deeper tissues25 and there are conflicting results regarding transcutaneous electrical nerve stimulation for labour pain26,27. An intense, more painful stimulation by transcutaneous electrical nerve stimulation and acupuncture may improve the analgesic effect, as more painful stimulation, irrespective of stimulation technique, may lead to ‘hyper-stimulation’ or ‘counterirritation’. This phenomenon was described by Melzack28 and may be effective if the stimulation is given near the painful site or at a distance. A similar phenomenon was described by Le Bars et al.29 as ‘diffuse noxious inhibitory controls’. Pain inhibition is not restricted to one specific segment, which suggests a more nonspecific pain modulation than the gate control mechanism. The reduced pain sensation is assumed to be achieved by inhibiting multireceptive neurones to the brain30. In the present study, the subcutaneous injections were shown to be less painful during administration than the intracutaneous injections—and ‘hyperstimulation’ supposedly lower—resulting in less pain relief. Recent clinical studies comparing the analgesic effects from subcutaneous versus intracutaneous injections of sterile water20, and sterile water versus saline injections11 do not confirm this. In fact, a minimum level of induced pain has not been defined. Moreover, the diffuse noxious inhibitory controls phenomenon mostly applies to pain from somatic afferents relieved by noxious stimulation in a distant part of the body, while pain from an intra-abdominal organ, such as the uterus during labour, is supplied by visceral afferents.
It is relevant to question whether the results from the present study would have been similar had women in active labour been included. Some data indicates that beta-endorphin plasma levels are higher at the end of the pregnancy31 and, because of this, baseline for pain tolerance might be raised. It may well be so, but it does not seem likely that this phenomenon alters the different responses to the two injection techniques.
In conclusion, because subcutaneous injections of sterile water seem to be less painful than the intracutaneous technique currently in use and are still efficient for analgesia20, we feel that the subcutaneous technique can be recommended as a modification of the technique, making it less painful to the patient.
The authors would like to thank Professor L. Terenius and Dr L. -E. Dyrehag for valuable advice when reviewing the paper and Ms E. Bergfeldt for her assistance during the data collection.